1. Field
The present invention relates to a composition comprising β-hydroxy-β-methylbutyrate (HMB) and methods of using HMB to enhance soft tissue healing and/or reduce recovery time from soft tissue trauma.
2. Background
Recovery of an animal from soft tissue trauma, including injuries to muscles, tendons and ligaments, typically requires significant time and cost. Acute soft tissue injury can occur during sports or physical activity or during simple everyday activities. Acute soft tissue trauma also includes the trauma that occurs during a surgical procedure, either related to repair of a soft tissue injury or unrelated to any injury and instead a result of cutting and/or manipulating soft tissue as part of any surgical procedure. Non-acute tissue injuries, such as sprains, also often require lengthy periods of rehabilitation and recovery. Even with appropriate supervision by a medical professional, healing of soft tissues can take a prolonged amount of time. These injuries can lead to delays in returning to regular activity and long-term weakness.
Soft tissue damage sustained from trauma, surgical procedures and falls are associated with increased morbidity and mortality in older adults. Recovery from soft tissue injuries often includes exercise and physical therapy and recovery may take six months or even more. Prolonged treatment is expensive and time-consuming. There is a need for a nutritional supplement to reduce recovery times, enhance soft tissue healing and enhance recovery after soft tissue trauma.
Animals such as horses, dogs and cats frequently sustain soft tissue trauma. By way of non-limiting example, it is very common for dogs to have soft tissue injuries that require surgical repair. Cruciate ligament surgeries such as TPLO (tibial-plateau-leveling osteotomy) or TTA (Tibial Tuberosity Advancement) surgery, hip replacements, and ruptured disc surgeries are commonly performed on animals. Recovery from these injuries and/or surgeries are difficult for both the pet and the owner. Owners typically have to assist the pet during walking and climbing stairs for weeks or months after surgery. Thus, the need exists for nutritional supplement that reduces the amount of time that the owner must assist the pet by days or weeks.
Alpha-ketoisocaproate (KIC) is the first major and active metabolite of leucine. A minor product of KIC metabolism is β-hydroxy-β-methylbutyrate (HMB). HMB has been found to be useful within the context of a variety of applications. Specifically, in U.S. Pat. No. 5,360,613 (Nissen), HMB is described as useful for reducing blood levels of total cholesterol and low-density lipoprotein cholesterol. In U.S. Pat. No. 5,348,979 (Nissen et al.), HMB is described as useful for promoting nitrogen retention in humans. U.S. Pat. No. 5,028,440 (Nissen) discusses the usefulness of HMB to increase lean tissue development in animals. Also, in U.S. Pat. No. 4,992,470 (Nissen), HMB is described as effective in enhancing the immune response of mammals. U.S. Pat. No. 6,031,000 (Nissen et al.) describes use of HMB and at least one amino acid to treat disease-associated wasting. HMB, combined with glutamine and arginine, has been found to increase wound collagen accumulation and improve skin wound repair.
The use of HMB to suppress proteolysis originates from the observations that leucine has protein-sparing characteristics. The essential amino acid leucine can either be used for protein synthesis or transaminated to the α-ketoacid (α-ketoisocaproate, KIC). In one pathway, KIC can be oxidized to HMB and this account for approximately 5% of leucine oxidation. HMB is superior to leucine in enhancing muscle mass and strength. The optimal effects of HMB can be achieved at 3.0 grams per day when given as calcium salt of HMB, or 0.038 g/kg of body weight per day, while those of leucine require over 30.0 grams per day.
Once produced or ingested, HMB appears to have two fates. The first fate is simple excretion in urine. After HMB is fed, urine concentrations increase, resulting in an approximate 20-50% loss of HMB to urine. Another fate relates to the activation of HMB to HMB-CoA. Once converted to HMB-CoA, further metabolism may occur, either dehydration of HMB-CoA to MC-CoA, or a direct conversion of HMB-CoA to HMG-CoA, which provides substrates for intracellular cholesterol synthesis. Several studies have shown that HMB is incorporated into the cholesterol synthetic pathway and could be a source for new cell membranes that are used for the regeneration of damaged cell membranes. Human studies have shown that muscle damage following intense exercise, measured by elevated plasma CPK (creatine phosphokinase), is reduced with HMB supplementation within the first 48 hrs. The protective effect of HMB lasts up to three weeks with continued daily use. Numerous studies have shown an effective dose of HMB to be 3.0 grams per day as CaHMB (calcium HMB) (˜38 mg/kg body weight-day−1). This dosage increases muscle mass and strength gains associated with resistance training, while minimizing muscle damage associated with strenuous exercise. HMB has been tested for safety, showing no side effects in healthy young or old adults. HMB in combination with L-arginine and L-glutamine has also been shown to be safe when supplemented to AIDS and cancer patients.
Recently, HMB free acid, a new delivery form of HMB, has been developed. This new delivery form has been shown to be absorbed quicker and have greater tissue clearance than CaHMB. The new delivery form is described in U.S. Patent Publication Serial No. 20120053240 which is herein incorporated by reference in its entirety.
While it is known that HMB supplementation can also prevent or lessen muscle loss during long periods of inactivity, such as hospitalization, prior to the present invention it was unknown that administration of HMB to a mammal with soft tissue trauma, whether from acute injury such as a soft tissue tear or rupture or surgery or non-acute soft tissue damage, results in faster repair and/or recovery of the soft tissue trauma and enhanced recovery from the injury or surgery.
The present invention comprises a composition of HMB and methods of use of HMB to result in enhanced recovery from soft tissue trauma. The enhanced recovery can include enhanced soft tissue healing subsequent to trauma or injury, including the soft tissue trauma that results from surgical procedures. The enhanced recovery also includes a more rapid recovery than expected. The present invention comprises a composition of HMB and methods of use of HMB to result in soft tissue repair and regeneration subsequent to soft tissue trauma or injury, including the soft tissue trauma that results from surgical procedures.